Assessment of the optimization of affinity and specificity at protein–DNA interfaces
By Justin Ashworth, David Baker. 2009
45 citations recorded by the source corpus.
The biological functions of DNA-binding proteins often require that they interact with their targets with high affinity and/or high specificity. Here, we describe a computational method that estimates the extent of optimization for affinity and specificity of amino acids at a protein–DNA interface based on the crystal structure of the complex, by modeling the changes in binding-free energy associated with all individual amino acid and base substitutions at the interface. The extent to which residues are predicted to be optimal for specificity versus affinity varies within a given protein–DNA interface and between different complexes, and in many cases recapitulates previous experimental observations. The approach provides a complement to traditional methods of mutational analysis, and should be useful for rapidly formulating hypotheses about the roles of amino acid residues in protein–DNA interfaces.
Subfields: Materials Chemistry, Molecular Biology
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Materials Chemistry
- David Baker
- Jeffrey J. Gray
- Tanja Kortemme
- Jens Meiler
- Brian Kuhlman
- Andrew Leaver-Fay
- Julia Koehler Leman
- Philip Bradley
In Molecular Biology
- David Baker
- Jeffrey J. Gray
- Tanja Kortemme
- Jens Meiler
- Brian Kuhlman
- Brian D. Weitzner
- Andrew Leaver-Fay
- Sergey Lyskov
Citations in the corpus
- Better together: Elements of successful scientific software development in a distributed collaborative community (2020, methodology): “The Robetta server[54] was deployed in 2003 and is commonly used by scientists inside and outside of our community for fragment generation[55], domain parsing and structure prediction[56,57], alanine scanning[58], and DNA interface scanning[59].”
- Computational reprogramming of homing endonuclease specificity at multiple adjacent base pairs (2010, methodology): “The specificities of all design models were calculated as a Boltzmann occupancy of the target complex, versus a partition function consisting of all competing single base pair variant sites (20).”